内容紹介
Treatment with Carbon-Ion Radiotherapy and Its Combinations―Basic Biological Studies and Investigations at the National Institute of Radiological Sciences
Summary
The clinical application of carbon ions generated by the heavy ion medical accelerator in Chiba(HIMAC)reached its 20th anniversary in 2014. More than 9,000 cancer patients have been treated at the National Institute of Radiological Sciences(NIRS). Carbon-ion radiotherapy has been applied for treating various types of tumors that were considered difficult to control with existing modalities. Our experience to date has indicated that carbon-ion radiotherapy is advantageous for head and neck cancer, non-small cell lung cancer, pancreatic cancer, prostate cancer, bone/soft tissue sarcomas of the pelvis, uterine cervix adenocarcinomas, and other cancers. However, some cancer types(such as those in close proximity to radiosensitive normal organs)require additional treatments to sensitize the target cancer because of limitation of the irradiation dose. Furthermore, systemic combined therapy is also utilized to suppress possible metastasis. Currently, some anticancer agents are utilized with carbon-ion radiotherapy, including dacarbazine, nimustine hydrochloride, vincristine(DAV), gemcitabine, cisplatin, and 5-fluorouracil. Interesting reagents such as PARP and HSP90 inhibitors have been proposed as cancer-cell-specific sensitizers for carbon-ion irradiation during basic biological studies, especially those from the Research Project with Heavy Ions at NIRS-HIMAC. In our laboratory, we have focused our studies on the suppression of metastasis. We have proposed the concurrent use of reagents to inhibit the invasive potential of cancer cells under carbon-ion irradiation. Recently, we have also shown that combining carbon-ion radiotherapy with the local injection of dendritic cells inhibits lung metastases in an in vivo murine model.
要旨
医療用重粒子加速装置(heavy ion medical accelerator in Chiba: HIMAC)から得られる炭素イオン線を使った癌治療は,治療開始から20周年となった2014年には治療患者数は9,000例を超え,多くの癌で高い局所制御率が得られることが示されている。しかしながら,癌の種類や形状,リスク臓器との位置関係によっては増感作用をもつ抗癌剤との併用が選択肢にあがる。また,転移の抑制が必要な場合も全身性併用療法の検討が必要である。現在臨床では,dacarbazine,nimustine hydrochloride,vincristine(DAV),ゲムシタビン(gemcitabine),シスプラチン(cisplatin),フルオロウラシル(5-fluorouracil)の併用が実施されている。一方,これまでの基礎研究ではADPリボースポリメラーゼ阻害剤やHSP90阻害剤の効果的な増感作用が報告されている。また,われわれは放射線に応答した癌細胞の浸潤能変化にかかわるパスウェイを解析し,特定の分子群を同時に阻害することによる浸潤抑制効果を示した。さらにマウス腫瘍モデルを用いた炭素イオン線治療樹状細胞併用療法の転移抑制効果についても紹介する。
目次
Summary
The clinical application of carbon ions generated by the heavy ion medical accelerator in Chiba(HIMAC)reached its 20th anniversary in 2014. More than 9,000 cancer patients have been treated at the National Institute of Radiological Sciences(NIRS). Carbon-ion radiotherapy has been applied for treating various types of tumors that were considered difficult to control with existing modalities. Our experience to date has indicated that carbon-ion radiotherapy is advantageous for head and neck cancer, non-small cell lung cancer, pancreatic cancer, prostate cancer, bone/soft tissue sarcomas of the pelvis, uterine cervix adenocarcinomas, and other cancers. However, some cancer types(such as those in close proximity to radiosensitive normal organs)require additional treatments to sensitize the target cancer because of limitation of the irradiation dose. Furthermore, systemic combined therapy is also utilized to suppress possible metastasis. Currently, some anticancer agents are utilized with carbon-ion radiotherapy, including dacarbazine, nimustine hydrochloride, vincristine(DAV), gemcitabine, cisplatin, and 5-fluorouracil. Interesting reagents such as PARP and HSP90 inhibitors have been proposed as cancer-cell-specific sensitizers for carbon-ion irradiation during basic biological studies, especially those from the Research Project with Heavy Ions at NIRS-HIMAC. In our laboratory, we have focused our studies on the suppression of metastasis. We have proposed the concurrent use of reagents to inhibit the invasive potential of cancer cells under carbon-ion irradiation. Recently, we have also shown that combining carbon-ion radiotherapy with the local injection of dendritic cells inhibits lung metastases in an in vivo murine model.
要旨
医療用重粒子加速装置(heavy ion medical accelerator in Chiba: HIMAC)から得られる炭素イオン線を使った癌治療は,治療開始から20周年となった2014年には治療患者数は9,000例を超え,多くの癌で高い局所制御率が得られることが示されている。しかしながら,癌の種類や形状,リスク臓器との位置関係によっては増感作用をもつ抗癌剤との併用が選択肢にあがる。また,転移の抑制が必要な場合も全身性併用療法の検討が必要である。現在臨床では,dacarbazine,nimustine hydrochloride,vincristine(DAV),ゲムシタビン(gemcitabine),シスプラチン(cisplatin),フルオロウラシル(5-fluorouracil)の併用が実施されている。一方,これまでの基礎研究ではADPリボースポリメラーゼ阻害剤やHSP90阻害剤の効果的な増感作用が報告されている。また,われわれは放射線に応答した癌細胞の浸潤能変化にかかわるパスウェイを解析し,特定の分子群を同時に阻害することによる浸潤抑制効果を示した。さらにマウス腫瘍モデルを用いた炭素イオン線治療樹状細胞併用療法の転移抑制効果についても紹介する。